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通过对数组 CRISPR 筛选的计算分析向药物研发管道输送稳健的候选药物。

Delivering Robust Candidates to the Drug Pipeline through Computational Analysis of Arrayed CRISPR Screens.

机构信息

Data Sciences & Quantitative Biology, Discovery Sciences, R&D, AstraZeneca, Cambridge, UK.

Discovery Biology, Discovery Sciences, R&D, AstraZeneca, Cambridge, Cambridgeshire, UK.

出版信息

SLAS Discov. 2020 Jul;25(6):646-654. doi: 10.1177/2472555220921132. Epub 2020 May 12.

DOI:10.1177/2472555220921132
PMID:32394775
Abstract

Genome-wide arrayed CRISPR screening is a powerful method for drug target identification as it enables exploration of the effect of individual gene perturbations using diverse highly multiplexed functional and phenotypic assays. Using high-content imaging, we can measure changes in biomarker expression, intracellular localization, and cell morphology. Here we present the computational pipeline we have developed to support the analysis and interpretation of arrayed CRISPR screens. This includes evaluating the quality of guide RNA libraries, performing image analysis, evaluating assay results quality, data processing, hit identification, ranking, visualization, and biological interpretation.

摘要

全基因组靶向 CRISPR 筛选是一种强大的药物靶点鉴定方法,因为它可以使用各种高度多重化的功能和表型测定来探索单个基因扰动的影响。通过高内涵成像,我们可以测量生物标志物表达、细胞内定位和细胞形态的变化。在这里,我们展示了我们开发的支持分析和解释靶向 CRISPR 筛选的计算流程。这包括评估向导 RNA 文库的质量、进行图像分析、评估测定结果的质量、数据处理、命中识别、排序、可视化和生物学解释。

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